Abstract
Epithelial neutophil activating peptide-78 (ENA-78)/CXCL-5 is a member of CXC chemokines. ENA-78 was originally described as a factor produced by epithelial cells only. But other types of cells including vascular endothelial cells also produce it. ENA-78 production by endothelial cells may be important for the regulation of neutrophil activation in inflammatory reactions. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA, which mimics the viral infection when applied to cells and affects the expression of various genes related to inflammatory reactions. In the present study, we examined the effect of poly IC on the expression of ENA-78 in human umbilical vein endothelial cells (HUVEC). HUVEC in culture were treated with poly IC and the expression of ENA-78 mRNA and protein were analyzed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Poly IC induced ENA-78 expression in time- and concentration-dependent manners. Th2-type cytokine IL-4 partially inhibited the induction of ENA-78 by poly IC. 2-Aminopurine, an inhibitor of dsRNA-dependent kinase, suppressed the induction of ENA-78 by poly IC. ENA-78 may be involved in the inflammatory reactions elicited by viral infection in endothelial cells.
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REFERENCES
Walz, A., R. Burgener, B. Car, M. Baggiolini, S. L. Kunkel, and P. M. Strieter. 1991. Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to inter-leukin 8. J. Exp. Med. 174:1355–1362.
Schnyder-Candrian, S., and A. Walz. 1997. Neutrophil-activating protein ENA-78 and IL-8 exhibit different patterns of expression in lipopolysaccharide-and cytokine-stimulated human monocytes. J. Immunol. 158:3888–3894.
Keates, S., A. C. Keates, E. Mizoguchi, A. Bhan, and C. P. Kelly. 1997. Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis. Am.J.Physiol. 273:G75–G82.
Imaizumi, T., K. H. Albertine, D. L. Jicha, T. M. McIntyre, S. M. Prescott, and G. A. Zimmerman. 1997. Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling of PMN adhesion. Am. J. Respir. Cell Mol. Biol. 17:181–192.
Nasu, K., K. Arima, K. Kai, K. Fujisawa, M. Nishida, and I. Miyakawa. 2001. Expression of epithelial neutrophil-activating peptide 78 in cultured human endometrial stromal cells. Mol. Hum. Reprod. 7:453–458.
Suzuki, S., M. Kobayashi, K. Chiba, I. Horiuchi, J. Wang, T. Kondoh, S. Hashino, J. Tanaka, M. Hosokawa, and M. Asaka. 2002. Autocrine production of epithelial cell-derived neutrophil attractant-78 induced by granulocyte colony-stimulating factor in neutrophils. Blood 99:1863–1865.
Fillmore, R. A., S. E. Nelson, R. N. Lausch, J. E. Oakes. 2003. Differential regulation of ENA-78 and GCP-2 gene expression in human corneal keratocytes and epithelial cells. Invest. Ophthalmol. Vis. Sci. 44:3432–3437.
Bozic, C. R., N. P. Gerard, and C. Gerard. 1996. Receptor binding specificity and pulmonary gene expression of the neutrophil-activating peptide ENA-78. Am. J. Resp. Cell Mol. 14:302–308.
Z'Graggen, K., A. Walz, L. Mazzucchelli, R. M. Strieter, and C. Mueller. 1997. The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease. Gastroenterology 113:808–816.
Rieder, G., W. Einsiedl, R. A. Hatz, M. Stolte, G. A. Enders, and A. Walz. 2001. Comparison of CXC chemokines ENA-78 and interleukin-8 expression in Helicobacter pylori-associated gastritis. Infect. Immun. 69:81–88.
Koch, A. E., M. V. Volin, J. M. Woods, S. L. Kunkel, M. A. Connors, L. A. Harlow, D. C. Woodruff, M. D. Burdick, and R. M. Strieter. 2001. Regulation of angiogenesis by the C-X-C chemokines interleukin-8 and epithelial neutrophil activating peptide 78 in the rheumatoid joint. Arthritis Rheum. 44:31–40.
Donninger, H., R. Glashoff, H. M. Haitchi, J. A. Syce, R. Ghildyal, E. van Rensburg, and P. G. Bardin. 2003. Rhinovirus induction of the CXC chemokine epithelial neutrophil activating peptide 78 in bronchial epithelium. J. Infect. Dis. 187:1809–1817.
Imaizumi, T., M. Kumagaia, M. Hatakeyama, W. Tamo, K. Yamashita, H. Yoshida, H. Munakata, and K. Satoh. 2003. Effect of 15-deoxy-Δ12 14-prostaglandin J2 on IL-1-induced expression of epithelial neutrophil-activating protein-78 in human endothelial cells. Prostaglandins Leukot. Essent. Fatty Acids. 69: 323–327.
Offermann, M. K., J. Zimring, K. H. Mellits, M. K. Hagan, R. Shaw, R. M. Medford, M. B. Mathews, S. Goodbourn, and R. Jagus. 1995. Activation of the double-stranded-RNA-activated protein kinase and induction of vascular cell adhesion molecule-1 by poly(I).poly(C) in endothelial cells. Eur. J. Biochem. 232:28–36.
Williams, B. R. 1999. PKR; a sentinel kinase for cellular stress. Oncogene 18:6112–6120.
Gale, M. Jr., and M. G. Katze. 1998. Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. Pharmacol. Ther. 78:29–46.
Zimmerman, G. A., R. E. Whatley, T. M. McIntyre, D. E. Benson, and S. M. Prescott. 1990. Endothelial cells for studies of platelet-activating factor and arachidonate metabolites. Methods Enzymol. 187:520–535.
Uetani, K., A. D. Der, M. Zamanian-Daryoush, C. Motte, B. Y. Lieberman, B. R. G. Williams, and S. C. Erzurum. 2000. Central role of double-stranded RNA-activated protein kinase in microbial inducetion of nitric oxide synthase. J. Immunol. 265: 988–996.
Gern, J. E., D. A. French, K. A. Grindle, R. A. Brockman-Schneider, S. Konno, and W. W. Busse. 2003. Double-stranded RNA induces the synthesis of specific chemokines by bronchial epithelial cells. Am. J. Resp. Mol. Cell. Biol. 28:731–737.
Heimeier, M. R., A. L. Scarim, and J. A. Corbett. 1998. Double-stranded RNA-induced inducible nitric-oxide synthase expression and interleukin-1 release by murine macrophages requires NF-Κ B activation. J. Biol. Chem. 273:15301–15307.
Steer, S. A., J. M. Moran, L. B. Maggi, R. M. L. Buller, H. Perlman, and J. A. Corbett. 2003. Regulation of cyclooxygenase-2 expres-sion by macrophages in response to double-stranded RNA and viral infection. J. Immunol. 170:1070–1076.
Zimmerman, G. A., T. M. McIntyre, and S. M. Prescott. 1996. Adhesion and signaling in vascular cell-cell interactions. J. Clin. Invest. 98:1699–1702.
Harcourt, J. L., M. K. Hagan, and M. K. Offerman. 2000. Moduration of double-stranded RNA-mediated gene induction by interferon in human umbilical vein endothelial cells. J. Interferon Cytokine Res. 20:1007–1013.
Ishikawa, A., T. Imaiuzmi, H. Yoshida, N. Nishi, T. Nakamura, M. Hirashima, and K. Satoh. 2004. Double-stranded RNA enhances the expression of galectin-9 in vascular endothelial cells. Immunol. Cell Biol. in press.
Kohoe, K. E., M. A. Brown, and F. Imani. 2001. Double-stranded RNA regulates IL-4 expression. J. Immunol. 167: 2496–2501.
Kumar, A., J. Haque, J. Lacoste, J. Hiscott, and B. R. Williams. 1994. Double-stranded RNA-dependent protein kinase activates transcription factor NF-Κ B by phosphorylating IΚ B. Proc. Natl. Acad. Sci. USA 91:6288–6292.
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Imaizumi, T., Hatakeyama, M., Taima, K. et al. Effect of Double-Stranded RNA on the Expression of Epithelial Neutrophil Activating Peptide-78/CXCL-5 in Human Endothelial Cells. Inflammation 28, 215–219 (2004). https://doi.org/10.1023/B:IFLA.0000049046.23377.44
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DOI: https://doi.org/10.1023/B:IFLA.0000049046.23377.44